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Background Glutamine family amino acids such as glutamate, pyroglutamate, and glutamine have been shown to play important roles in COVID-19. However, it is still unclear about the role of pyroglutamate in COVID-19. Thus, we use a two-sample Mendelian randomization (MR) study to identify the genetic causal link between blood pyroglutamine levels and COVID-19 risk. Methods Pyroglutamine genetic instrumental variables (IVs) were chosen from the largest pyroglutamine-associated genome-wide association studies (GWAS). The largest COVID-19 GWAS dataset was employed to evaluate the causal link between blood pyroglutamine levels and COVID-19 risk using two-sample MR analysis. Results We found no significant pleiotropy or heterogeneity of pyroglutamine-associated genetic IVs in COVID-19 GWAS. Interestingly, we found that as pyroglutamine genetically increased, the risk of COVID-19 decreased using inverse variance weighted (IVW) (Beta = − 0.644, p = 0.003; OR = 0.525, 95% CI [0.346–0.798]) and weighted median (Beta = − 0.609, p = 0.013; OR = 0.544, 95% CI [0.337–0.878]). Conclusion Our analysis suggests a causal link between genetically increased pyroglutamine and reduced risk of COVID-19. Thus, pyroglutamine may be a protective factor for patients with COVID-19.

Abdominal aortic aneurysm (AAA) is a permanent expansion of the abdominal aorta that has a high mortality but limited treatment options. Phosphodiesterase (PDE) 4 family members are cAMP-specific hydrolyzing enzymes and have four isoforms (PDE4A-PDE4D). Several pan-PDE4 inhibitors are used clinically. However, the regulation and function of PDE4 in AAA remain largely unknown. Herein, we showed that PDE4D expression is upregulated in human and angiotensin II-induced mouse AAA tissues using RT-PCR, western blotting, and immunohistochemical staining. Furthermore, smooth muscle cell (SMC)-specific Pde4d knockout mice showed significantly reduced vascular destabilization and AAA development in an experimental AAA model. The PDE4 inhibitor rolipram also suppressed vascular pathogenesis and AAA formation in mice. In addition, PDE4D deficiency inhibited caspase 3 cleavage and SMC apoptosis in vivo and in vitro, as shown by bulk RNA-seq, western blotting, flow cytometry and TUNEL staining. Mechanistic studies revealed that PDE4D promotes apoptosis by suppressing the activation of cAMP-activated protein kinase A (PKA) instead of the exchange protein directly activated by cAMP (Epac). Additionally, the phosphorylation of BCL2-antagonist of cell death (Bad) was reversed by PDE4D siRNA in vitro, which indicates that PDE4D regulates SMC apoptosis via the cAMP-PKA-pBad axis. Overall, these findings indicate that PDE4D upregulation in SMCs plays a causative role in AAA development and suggest that pharmacological inhibition of PDE4 may represent a potential therapeutic strategy.

Although individuals with coronavirus disease 2019 (COVID-19) are known to be at increased risk for other conditions resulting from pathogenic changes (including metaplastic or anaplastic) in the lungs and other organs and organ systems, it is still unknown whether COVID-19 affects childhood intelligence. The present two-sample Mendelian randomization study aims to identify the genetic causal link between COVID-19 and childhood intelligence. Four COVID-19 genetic instrumental variants (IVs) were chosen from the largest genome-wide association studies (GWAS) for COVID-19 (hospitalized vs. population) (6406 cases and 902 088 controls of European ancestry). The largest childhood intelligence GWAS (n = 12 441 individuals of European ancestry) was used to evaluate the effect of the identified COVID-19-associated genetic IVs on childhood intelligence. We found that as the genetic susceptibility to COVID-19 increased, childhood intelligence followed a decreasing trend, according to mr_egger (β = -0.156; p = 0.601; odds ratio [OR] = 0.856; 95% confidence interval [CI]: 0.522-1.405), simple mode (β = -0.126; p = 0.240; OR = 0.882; 95% CI: 0.745-1.044), and weighted mode (β = -0.121; p = 0.226; OR = 0.886; 95% CI: 0.758-1.036) analyses. This trend was further demonstrated by the weighted median (β = -0.134; p = 0.031; OR = 0.875; 95% CI: 0.774-0.988) and the inverse variance weighted (β = -0.152; p = 0.004; OR = 0.859; 95% CI: 0.776-0.952). Our analysis suggests a causal link between genetically increased COVID-19 and decreased childhood intelligence. Thus, COVID-19 may be a risk factor for declines in childhood intelligence.

Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy. Here, we show that ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages (AMs). Then, AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs, thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation. This pH regulation is attributable to oxidized cholesterol, which is enriched in AO-MPs and translocated to endosomal membranes, thus interfering with proton pumps and impairing endosomal acidification. In addition to promoting viral degradation, AO-MPs also inhibit the proinflammatory phenotype of AMs, leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects. These findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future.

Thyroid cancer (TC) has increased globally, with a prominent increase in small, papillary thyroid cancers. PEST-containing nuclear protein (PCNP), a nuclear protein, has been found to be associated with human cancers in recent years. However, the role and molecular mechanism of PCNP in thyroid cancer remain underexplored. In the present study, the results showed that the expression levels of PCNP in human thyroid tissues were higher than those in adjacent non-tumor tissues. Overexpression of PCNP reduced the proliferation, migration, and invasion of human thyroid cancer cells and down-regulation of PCNP showed reverse effects. In addition, PCNP regulated cell cycle arrest through modifications in the expression of cell cycle regulating genes and PCNP affected apoptosis via activation of ERK/JNK/p38 pathway in thyroid cancer cells. Moreover, PCNP overexpression promoted autophagy by reducing the expression levels of Wnt/β-catenin pathway in TC cells, however, PCNP knockdown had opposite effects. Furthermore, PCNP overexpression reduced the growth of xenografted human thyroid cancer, whereas PCNP knockdown showed opposite trends. In conclusion

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

Background Hemoglobin A1c(HbA1c) is widely used to measure glycemic status and control in diabetes testing and treatment and is an important risk factor forcomplications of diabetes. Hemoglobin variants can interfere with the HbA1c testing method by reducing the life span of erythrocytes or due to differences in glycation degrees. In this study, glycation levels of the HbA, HbG-Coushatta, and HbG-Taipei β-chains (βA, βG-Coushatta, and βG-Taipei, respectively) were examined. Methods Blood samples from heterozygotic patients (HbG-Coushatta/HbA, HbG-Taipei/HbA) were analyzed. Glycation rateswere determined using high-performance liquid chromatography with tandem mass spectrometry. Ratios of glycated βG-Coushatta to glycated βA and glycated βG-Taipei to glycated βA were calculated by comparingareas under the curves from extracted ion chromatograms. Results βG-Coushatta and βG-Taipei were 6.08 ± 1.38% and 5.95 ± 0.93% glycated (respectively), which were significantly higher than βA chains(4.55 ± 1.30% and 4.51 ± 0.91%, respectively; p = 0.000). The total glycation degree (α + β) in HbG-Coushatta and HbG-Taipei heterozygotes were estimated to be 9% and 8% higher than those of HbA homozygotes (P＜0.001), respectively. Conclusion βG-Coushatta and βG-Taipei glycation degrees were significantly higher than βA, while the differences in total hemoglobin (α + β) were small and unlikely to impact the clinical interpretation of HbA1c results.

In order to explore the spatial and temporal changes in spatial patterns and source changes in heavy metals in Xiangzhou District, 395 and 326 soil samples were collected from cultivated soil in Xiangzhou District in November 2009 and November 2019, respectively. The contents of Cr, Pb, As, Hg, and Cd during these two years were measured. The spatial pattern and variation distribution of five types of heavy metals during these two years were obtained by using the empirical Bayesian Kriging (EBK) method. The effect (

Resveratrol (RES) is a polyphenol with diverse beneficial biological and pharmacological activities, and our previous results have demonstrated its neuroprotective effects in several metabolic diseases, including non-alcoholic fatty liver disease. The aim of the present study is to investigate the potential effect of RES against oleic acid (OA)-induced cell injuries in SH-SY5Y cells and explore the possible mechanism. Based on the dose- and time-dependent effects of OA on cell proliferation and LDH release, SH-SY5Y cells were challenged with OA and incubated with or without RES (10-5-10-9 mM) or sitagliptin (STG, 10-7 mM). Lipid accumulation, SREBP1 and PPARα protein expression, glucose consumption and IRS1, AKT, ERK phosphorylation under insulin stimulation, and ROS production were detected. The protein expression of brain-derived neurotrophic factor (BDNF), Copine 6, and key molecules in the Wnt/β-catenin signalling pathway were measured via western blot. The expression of Wnt 1 was also measured via immunofluorescence staining. The results showed that RES treatment could alleviate the neurotoxicity induced by OA, as indicated by the increased cell proliferation and the decreased concentration of LDH in the supernatant. The increased lipid deposition and protein expression of SREBP1 and PPARα induced by OA was also reversed by treatment with RES. Moreover, RES could upregulate glucose consumption and the protein expression of phosphorylated IRS1, AKT, ERK and reduced ROS production in OA-induced SH-SY5Y cells. Furthermore, RES treatment reversed the imbalanced protein expression of BDNF, Copine 6, p-β-catenin, and Wnt 1 in SH-SY5Y cells induced by OA and decreased the hyperexpression of p-GSK3β. However, these effects were suppressed by DKK1, which is a specific antagonist of the Wnt signalling pathway. These results suggested that RES has a neuroprotective effect against OA-induced cell injury and dysfunctional glucolipid metabolism, and the mechanism might involve its ability to regulate oxidative stress and insulin resistance via the Wnt/β-catenin signalling pathway.

Acquired resistance to glucocorticoids (GCs) is an obstacle to the effective treatment of leukemia, but the molecular mechanisms of steroid insensitivity have not been fully elucidated. In this study, we established an acquired GC-resistant leukemia cell model and found a long noncoding RNA, HOTAIRM1, was overexpressed in the resistant cells by transcriptional profiling, and was higher expressed in patients with poor prognosis. The whole-genome-binding sites of HOTAIRM1 were determined by ChIRP-seq (chromatin isolation by RNA purification combined with sequencing) analysis. Further study determined that HOTAIRM1 bound to the transcriptional inhibitory region of ARHGAP18 and repressed the expression of ARHGAP18, which led to the increase of RHOA/ROCK1 signaling pathway and promoted GC resistance through antiapoptosis of leukemia cells. The inhibition of ROCK1 in GC-resistant cells could restore GCs responsiveness. In addition, HOTAIRM1 could also act as a protein sequester to prevent transcription factor AML1(acute myeloid leukemia 1) from binding to the regulatory region of ARHGAP18 by interacting with AML1. At last, we also proved AML1 could directly activate the expression of HOTAIRM1 through binding to the promoter of HOTAIRM1, which enriched the knowledge on the regulation of lncRNAs. This study revealed epigenetic causes of glucocorticoid resistance from the perspective of lncRNA, and laid a foundation for the optimization of glucocorticoid-based leukemia treatment strategy in clinic.

A new species Andropromachus ynau sp. nov.. is described and the Chinese species of the moss-like stick insect genus Andropromachus are reviewed. An updated key to the known species of this genus is provided. Types of the new species are deposited in Yunnan Agricultural University (YNAU).

Myelodysplastic syndrome (MDS) is a malignant tumor of the hematological system characterized by long‐term, progressive refractory hemocytopenia. In addition, the risk of leukemia is high, and once it develops, the course of acute leukemia is short with poor curative effect. Animal models are powerful tools for studying human diseases and are highly effective preclinical platforms. Animal models of MDS can accurately show genetic aberrations and hematopoietic clone phenotypes with similar cellular features (such as impaired differentiation and increased apoptosis), and symptoms can be used to assess existing treatments. Animal models are also helpful for understanding the pathogenesis of MDS and its relationship with acute leukemia, which helps with the identification of candidate genes related to the MDS phenotype. This review summarizes the current status of animal models used to research myelodysplastic syndrome (MDS)., Animal models of myelodysplastic syndrome (MDS).

BACKGROUND: Acute cerebral infarction (ACI) is a common cerebrovascular disease in clinical practice. OBJECTIVE: The present study aims to investigate the efficacy and safety of alteplase and urokinase in treating ACI. METHODS: A total of 96 patients with ACI, who were treated with alteplase and urokinase, were selected as the main subjects. Among these patients, 45 patients with ultra-early acute cerebral infarction, who received intravenous thrombolysis with RT-PA (alteplase), were included in the treatment group, while 51 patients with acute cerebral infarction, who were treated with urokinase in the same time period, were included in the control group. RESULTS: The National Institute of Health Stroke Scale (NIHSS) scores were significantly lower in the treatment group and control group (P< 0.05) at two hours, seven days and 14 days after thrombolysis, when compared to those before thrombolysis. The bleeding rate was significantly lower in the control group, when compared to the treatment group (P< 0.05). CONCLUSION: The intravenous thrombolysis with urokinase or alteplase in the ultra-early stage of acute cerebral infarction can reduce the neurological injury symptoms and effectively improve the prognosis of patients with stroke. Urokinase is lower in risk of bleeding, but better in safety, when compared to alteplase.

Medicinal plant stem cells are separated from the meristem and vascular cambium of medicinal plants, which can produce active components for preventing and treating diseases and improving body physical functions under certain conditions. Medicinal plant stem cells come from a broad category of medicinal plants, including ethnic medicinal plants, folk medicinal plants, original plants of health products, vegetables, fruits, and other potential medicinal plants. At present, the techniques for the isolation, identification, preservation and culture of medicinal plant stem cells have become increasingly mature, and the mechanism of stem cell differentiation, growth and regulation of secondary metabolites has been studied in depth. Medicinal plant stem cells have a broad application prospect in medicine, health food, food and medical beauty products. As a strategic resource, the construction of thequot;Global Medicinal Plant Stem Cell Bankquot; was first proposed to preserve various kinds of medicinal plant resources in the world, and it will go global relying on the internationalization strategy of traditional Chinese medicine. The bank should follow safety, environmental protection, advanced and practical design principles. The main construction contents include the original plant bank, stem cell bank, component resource bank, gene bank, database and resource sharing system, with genetic and data resources incorporated into the scope of protection and utilization. The bank will establish a new strategy for medicinal plant resources protection and regeneration, and provide a new resource for natural products drug discovery and a technology sharing platform for various medicinal plant stem cells. As a resource treasury, a source of innovative technologies and a center of cooperation, it will become the core driving force of the global medicinal plant stem cell industry.

Indoor airborne fungi have been associated with adverse human health effects. Therefore, it is important to understand the causes of underlying variation in airborne fungi in indoor environments. This study consequently aimed to investigate the association between indoor fungi with temporal variation, environmental parameters, and potential confounders over 10 months in four library rooms using Andersen samplers. Indoor fungal concentrations peaked in October and were lowest in March in both stack rooms, whereas the highest concentrations in both reading rooms were observed in September with lowest concentrations in July. Nonparametric analyses revealed higher fungal concentrations in the rooms that were significantly associated with relative humidity ≥ 60%, PM2.5 ≥ 35 μg/m3, number of people ≥ 16, open windows, working air conditioners, and room area

Melatonin has significant inhibitory effects in numerous cancers, especially breast cancer. In estrogen receptor (ER)-positive human breast cancer, the oncostatic actions of melatonin are mainly achieved by suppressing ER mRNA expression and ER transcriptional activity via the MT1 receptor. Melatonin also regulates the transactivation of nuclear receptors, estrogen-metabolizing enzymes, and the expression of related genes. Furthermore, melatonin suppresses tumor aerobic glycolysis, critical cell-signaling pathways relevant to cell proliferation, survival, metastasis, and overcomes drug resistance. Studies in animal and human models indicate that disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer, resulting in resistance to hormone therapy and chemotherapy, which may be reversed by melatonin.

Unlike general ventilation, personalized ventilation can improve thermal comfort and conserve energy based on individual differences. It can also provide every individual the ability to control fresh air exposure and ensure good indoor air quality. However, determining how to improve air supply efficiency while avoiding a draft sensation is still a difficult question. This paper introduces a body movement-based personalized targeted air supply device. Two indices, size target value T s and velocity target value T r , are introduced to evaluate the degree to which the created flow field reaches the desired level. Additionally, the air supply effect of the device is compared with that of other devices. This research shows that the personalized targeted air supply device can successfully deliver air to the target area and improve air supply accessibility in the target area. The multinozzle coupling air supply mode produces a flow field air velocity of approximately 0.3 m/s, thus effectively avoiding a draft sensation. Compared with that of other personalized nozzles, the energy consumption is reduced significantly, by 88.2%, while the air supply accessibility can be increased by 48% with equivalent energy consumption.

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a nucleic acid-binding protein. Reportedly, hnRNPK is overexpressed in many human tumors, and such overexpression is associated with poor prognosis, implicating the role of hnRNPK as an oncogene during tumorigenesis. In this study, hnRNPK expression in lung cancer tissues was investigated.Briefly, hnRNPK was knocked down in lung cancer cell lines, and effects of knockdown on the cell proliferation, migration, and cell cycle were assessed using a cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assay and flow cytometry. The effects of hnRNPK knockdown on the p53-dependent signaling pathway were examined using western blotting. Finally, the effect of hnRNPK knockdown on tumor growth was verified in vivo using a lung cancer xenograft mouse model.hnRNPK knockdown inhibited the cell proliferation, migration and cell cycle. In addition to phenotypic changes, hnRNPK knockdown upregulated expressions of pCHK1, pCHK2, and p53，p21，cyclin D1, thereby mediating the DNA damage response (DDR). The regulatory function of hnRNPK during p53/p21/cyclin D1 signaling in hnRNPK-knockdown A549 cells was confirmed by suppressed the protein expression of associated signaling pathways, which inhibited DDR.hnRNPK plays a crucial role in the progression of lung cancer, ultimately affecting survival rate. Inhibition of progression of lung cancer cells induced by hnRNPK-knockdown is dependent on activation of p53 by the p53/p21/cyclin D1 pathway.

Regulatory T cells (Tregs) are a subset of CD4+T cells with their immunosuppressive activities to block abnormal or excessive immune responses to self and non-autoantigens. Tregs express the transcription factor Foxp3, maintain the immune homeostasis, and prevent the initiation of anti-tumor immune effects in various ways as their mechanisms to modulate tumor development. Recognition of different phenotypes and functions of intratumoral Tregs has offered the possibilities to develop therapeutic strategies by selectively targeting Tregs in cancers with the aim of alleviating their immunosuppressive activities from anti-tumor immune responses. Several Treg-based immunotherapeutic approaches have emerged to target cytotoxic T lymphocyte antigen-4, glucocorticoid-induced tumor necrosis factor receptor, CD25, indoleamine-2, 3-dioxygenase-1, and cytokines. These immunotherapies have yielded encouraging outcomes from preclinical studies and early-phase clinical trials. Further, dual therapy or combined therapy has been approved to be better choices than single immunotherapy, radiotherapy, or chemotherapy. In this short review article, we discuss our current understanding of the immunologic characteristics of Tregs, including Treg differentiation, development, therapeutic efficacy, and future potential of Treg-related therapies among the general cancer therapy.

The Coronavirus disease 2019 (COVID-19) pandemic has resulted in significant delays and cost overrun in construction projects. The implementation of health and safety (H&S) technologies is one of the most important strategies to alleviate the adverse impacts of COVID-19 on the construction industry and help the industry adapt to the new normal. This study aims to evaluate the adoption of H&S technologies for pandemic management in the construction sector under the COVID-19 pandemic. Semi-structured interviews with eighteen practitioners engaged from construction companies and technology firms were conducted to collect their views on the driving forces and issues of the adoption of H&S technologies for pandemic management in Chinese construction projects. The results reveal that the major H&S technologies used included the health quick response (QR) code system, artificial intelligence (AI)-powered fever monitoring, and site access control system. These technologies were reported to be effective in preventing the spread of the pandemic in workplaces. The findings of the study amplify that the pandemic may serve as an acceleration of the adoption of H&S technologies in the construction sector. Other technologies, such as building information modeling, drones, AI-based safety monitoring, and robotics, however, were seldom used in the studied projects. The interviewees addressed several problems regarding the implementation of these technologies. High costs of technologies, a lack of client support, and disruptions to the normal work process were the main hurdles of the adoption of these technologies. The results indicated that the external influence factor—the COVID-19 pandemic—could considerably drive the use of H&S technologies, whereas the internal influence factors—cost and compatibility of technology—might be the major barriers to technology adoption. To encourage the wider use of H&S technologies in construction, the government is recommended to support the technology transformation by granting financial subsidies for costs involved in innovation adoption. Project owners may consider investing substantially in H&S technologies that can strengthen their resilient and innovative ability to adapt to the post-COVID-19 landscape. The present results will be useful to industry stakeholders and researchers interested in developing H&S technologies for combating the COVID-19 pandemic and future crises.

BackgroundMyelin oligodendrocyte glycoprotein-antibody (MOG-ab)-associated disease (MOGAD) has highly heterogenous clinical and imaging presentations, in which encephalitis is an important phenotype. In recent years, some atypical presentations in MOG-ab-associated encephalitis (MOG-E) have been increasingly reported but have not yet been described well. The aim of the study was to describe the clinical and imaging features of patients with MOG-E in our center. Atypical phenotypes would be reported, which is expected to expand the spectrum of MOGAD.MethodsWe reviewed medical records of 59 patients with MOGAD diagnosed in our center and identified cases who had ever experienced encephalitic symptoms. Three hundred ten patients with autoimmune encephalitis (AE) were also reviewed, and cases with positive MOG-ab were identified. Besides, patients with chronically progressive encephalitis were identified from 13 MOG-E and 310 AE patients. We collected demographic, clinical, laboratory, radiological, and outcome data to explore clinical and imaging characteristics in MOG-E, especially in the atypical phenotype of chronically progressive encephalitis.ResultsWe identified 13 patients (7 males, 6 females) with MOG-E. The median age at onset was 33 years (range 13~62 years). Most (9/13, 69.2%) of patients showed acute or subacute onset of encephalitic symptoms. Brain MRI abnormalities were observed in all patients. The most common lesion locations on MRI were cortical/subcortical (11/13, 84.6%), deep/periventricular white matter (10/13, 76.9%) and corpus callosum (4/13, 30.8%). Brain MRI patterns were categorized into four phenotypes. The most common pattern was cortical encephalitis with leptomeningeal enhancement/brain atrophy (10/13, 76.9%). Eight (8/13, 61.5%) patients had a good response to immunotherapy. Four (4/13, 30.8%) patients with chronically progressive course were identified from MOG-E cohort. They showed leukodystrophy-like pattern, multifocal hazy lesions, or cortical encephalitis on MRI. With immunotherapy, they only showed mild or no improvement. We also identified four (4/310, 1.3%) patients with chronically progressive course from AE cohort. They had better outcomes than counterparts in MOG-E.ConclusionsThis study demonstrates that encephalitic presentations in MOGAD had complex clinical patterns. Chronically progressive encephalitis may be a new phenotype of MOGAD. We recommend to test MOG-ab in subacute and chronic progressive dementia with leukodystrophy-like MRI lesions.

We report a protocol for obtaining high-quality single-cell transcriptomics data from human lung biospecimens acquired from core needle biopsies, fine-needle aspirates, surgical resection, and pleural effusions. The protocol relies upon the brief mechanical and enzymatic disruption of tissue, enrichment of live cells by fluorescence-activated cell sorting (FACS), and droplet-based single-cell RNA sequencing (scRNA-seq). The protocol also details a procedure for analyzing the scRNA-seq data. For complete details on the use and execution of this protocol, please refer to Chan et al. (2021).

To resolve the ongoing debate on the role of plasma omega-3 fatty acids in rheumatoid arthritis (RA), we attempted to identify the association between omega-3 intake and the risk of RA.We analyzed data from the largest genome-wide association study (GWAS) for omega-3 fatty acids (N = 114,999 of European ancestry) and RA (14,361 cases and 43,923 controls of European ancestry). Mendelian randomization-egger_intercept, MR-PRESSO, and Cochran's Q test were used to determine pleiotropy and heterogeneity. Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode were used to evaluate the causal association of plasma omega-3 levels on RA.We found no significant pleiotropy, heterogeneity, and bias among the omega-3 genetic instrumental variables (IVs) in RA GWAS datasets. MR analysis demonstrated that as omega-3 levels genetically increased, the risk of MS increased using MR-egger (Beta = 0.137, p = 0.037; OR = 1.146, 95% CI: [1.014, 1.296]), weighted median (Beta = 0.162, p = 0.001; OR = 1.176, 95% CI: [1.070, 1.292]), IVW (Beta = 0.102, p = 0.025; OR = 1.108, 95% CI: [1.013, 1.211]), simple mode (Beta = 0.219, p = 0.149; OR = 1.245, 95% CI: [0.931, 1.665]), and weighted mode (Beta = 0.146, p = 0.006; OR = 1.157, 95% CI: [1.051, 1.274]).Our analysis suggested a causal association between genetically increased plasma omega-3 levels and the increased risk of RA in populations with European ancestry. Thus, to reduce the risk of RA, those of European descent should reduce omega-3 intake. Key Points • No significant pleiotropy or heterogeneity among the omega-3 genetic IVs in RA GWAS datasets. • Genetically increased plasma omega-3 levels enhanced the risk of RA in European lineages.

Background We report a mononucleosis-like illnesses case due to co-infection with severe fever with thrombocytopenia syndrome virus (SFTSV) and spotted fever group rickettsia (SFGR), which to the best of our knowledge, has never been reported . Case presentation A 64-year-old male with an 11-day history of fever, sore throat, malaise, nausea, and non-pruritic rash was admitted to our emergency department. Prior to admission, he was bitten by ticks. Laboratory tests revealed a white blood cell count of 24,460 cells/μL with 25% atypical lymphocytes and 20% mononucleosis, thrombocytopenia. Test results were positive for SFTSV RNA, SFTSV-specific IgM antibody, and SFGR-specific IgM antibody. He was diagnosed with mononucleosis-like illnesses due to co-infection with SFTSV and SFGR. After administration of doxycycline, he recovered completely. Conclusions The clinical presentation may be atypical in co-infection with SFTSV and SFGR. This finding highlighted the importance of considering SFGR infection, as well as a SFSTV and SFGR co-infection for the differential diagnosis of patients bitten by ticks in SFTSV-endemic areas.

Little is known about the disease burden, health-care resource utilization (HCRU), or treatment of patients with generalized pustular psoriasis (GPP) in Japan. This retrospective cohort study used data from the Japanese Medical Data Center database to compare the demographics, comorbidities, and medication use of patients with GPP and plaque psoriasis and estimate their all-cause HCRU. The patient selection period was from January 1, 2015 to December 31, 2019, and patients must have had at least one confirmed inpatient claim or outpatient claim for GPP or plaque psoriasis. During the 12-month follow-up period, 110 patients with GPP and 20,254 patients with plaque psoriasis were identified. An age- and sex-matched (4:1) comparator control cohort, including members of the general population without a diagnosis of psoriasis (but allowing for a diagnosis of psoriatic arthritis), GPP, or palmoplantar pustulosis, was used. The most prevalent comorbidities in patients with GPP included allergic rhinoconjunctivitis, hypertension, and peptic ulcer disease. Patients with GPP were more likely to experience more comorbidities than those with plaque psoriasis, including asthma, chronic obstructive pulmonary disease, interstitial pneumonia, hyperuricemia and gout, tonsillitis, psoriatic arthritis, other psoriasis, and osteoporosis. Patients with GPP were more likely to be treated with a combination therapy than those with plaque psoriasis (65.5% vs 21.7%, respectively) and less likely to be treated with a topical medication alone (20.9% vs 50.8%). Patients with GPP had more outpatient visits than patients in the plaque psoriasis or matched control cohorts (mean [standard deviation], 14.8 [8.3] vs 11.0 [7.6] and 7.8 [7.2], respectively). They were also more likely to require inpatient hospitalization (24.5% vs 6.4% and 5.0%, respectively). Despite study limitations, patients with GPP in Japan were found to have a higher disease burden, including presence of comorbidities and medication use, than those with plaque psoriasis.

Background: To investigate the prevalence of falls and associated factors among older adults in urban and rural areas and to facilitate the design of fall prevention interventions. Methods: We used cluster random sampling to investigate the sociodemographic information, living habits, medical status, falls, home environment, and balance ability among 649 older adult participants. Univariate and multivariate logistic regression were used to examine the associated factors of falls. Results: The incidence of falls among older adults in Shantou City was 20.65%. Among them, the incidence was 27.27% in urban areas and 16.99% in rural areas. The rate of injury from falls among older adults was 14.48%, with18.61% in urban area and 12.20% in rural area. Multivariate analysis showed that the associated factors of falls among older adults in Shantou City included a high school or below education level (OR = 2.387, 95% CI: 1.305–4.366), non-farming as the previous occupation (OR = 2.574, 95% CI: 1.613–4.109), incontinence(OR = 2.881, 95% CI: 1.517–5.470), lack of fall prevention education (OR = 1.856, 95% CI: 1.041–3.311), and reduced balance ability (OR = 3.917, 95% CI: 2.532–6.058). Discussion: Older adults have a higher rate of falling in Shantou City, compared to the average rate in China. There are similarities and differences in the associated factors of falls among older adults between urban and rural areas of Shantou City. Targeted interventions for older adults in different regions may be more effective in reducing the risk of falls.

CircRNA derived from vacuolar ATPase assembly factor (circVMA21) is a newly-researched circRNA, which is reported to adjust the degeneration of intervertebral disc. But, function of circVMA21 in infantile pneumonia is yet to be explored. The research surveyed the role of circVMA21 in lipopolysaccharide (LPS)-caused WI-38 cell inflammatory injury. LPS (10 μg/ml, 12 hr) was exploited to arouse WI-38 cell inflammatory injury. Subsequently, the mediatory impacts of microRNA (miR)-142-3p and circVMA21 in LPS-evoked cell injury were detected after transfection with the inhibited or overexpressed vectors. In above processes, cell behaviors of cell viability, apoptosis, and pro-inflammatory factors were monitored. NF-κB and JNK pathways were elucidated to showcase the feasible molecular mechanisms. Results displayed that LPS engendered WI-38 cell inflammatory injury was alleviated as well as activated NF-κB and JNK pathways was interdicted by miR-142-3p suppression. Importantly, restrained miR-142-3p expression was discovered in WI-38 cells after overexpressing circVMA21. Moreover, overexpressed circVMA21 exerted the similar functions as miR-142-3p suppression in LPS-triggered WI-38 cell injury. But, the influence was clearly reversed by miR-142-3p overexpression. Hindered NF-κB and JNK pathways caused by overexpressed circVMA21 was also crippled by miR-142-3p overexpression. The research discolsed that circVMA21 protected WI-38 cells to resist LPS-triggered inflammatory injury via miR-142-3p-NF-κB/JNK axis.

Ossification of ligamentum flavum (OLF) is the leading cause of progressive thoracic myelopathy (TM) in East Asian countries. Surgical decompression is the general treatment for TM. This study investigated the application of percutaneous full endoscopic posterior decompression (PEPD) for the treatment of thoracic OLF. Eighteen patients with TM were treated by PEPD under local anaesthesia. Patients had an average age of 59.1 years and single-level lesions mostly at the lower thoracic vertebrae. Computed tomography and magnetic resonance imaging were used to classify the OLF. The pre- and postoperative neurological statuses were evaluated using the American Spinal Injury Association (ASIA) sensory and motor score, modified Japanese Orthopaedic Association (mJOA) score and Frankel grade. OLF for all patients was classed as lateral, extended, and enlarged types without comma and tram track signs. Decompression was completed, and a dome-shaped laminotomy was performed through limited laminectomy and flavectomy. Dural tears in 2 patients were the only observed complication. The average score of ASIA sensory and motor, mJOA, as well as the Frankel grade improved significantly after surgery at an average follow-up time of 17.4 months. The average recovery rate (RR) was 47.5% as calculated from the mJOA scores. According to RR, 10 cases were classified as good, 4 cases fair, and 4 cases unchanged. For patients with thoracic OLF at a single level and lateral, extended, and enlarged types without comma and tram track signs, it is safe and reliable to perform PEPD, which has satisfactory clinical results. These slides can be retrieved under Electronic Supplementary Material.

In this paper, based on the age, sex, disease type, and consultation time of dental emergency during COVID-19 epidemic, a comprehensive analysis of dental emergency management and prevention and control of COVID-19 was conducted.A total of 739 emergency dental cases were collected from January 29 2020 to February 28 2020. They were divided into 3 groups，including adolescents (≤18 years), young adults (18 ~ 60 years), and elderly ( ≥60 years old). The data was analyzed using SPSS 21.0 software package.The ratio of male to female was 1.24∶1. There were 655 emergency cases during the day and 84 cases during the night. The types of diseases included pericoronitis (15.83%), apical periodontitis (14.21%), pulpitis (13.40%), periodontitis (12.31%), oral mucosal disease (12.18%), Oral and maxillofacial trauma (10.55%), oral and maxillofacial space infection (8.39%), dental disease in children (5.41%), oral and maxillofacial tumors (2.84%), temporomandibular joint dislocations and disorders (1.76%), and others (3.11%).Under the epidemic situation of the new coronavirus, as one of the high-risk departments, it is of great significance to enhance the clinical emergency skills and ability of emergency treatment, improve patients' oral health awareness, address the diagnosis and treatment of essential diseases, for the improvement the quality of dental medical care and the prevention and control of COVID-19 epidemic.

Generalized pustular psoriasis (GPP) is a rare and severe systemic, neutrophilic skin disease. To date, accurate clinical profiling of patients with GPP remains poorly understood. In this study, we present the characteristics and estimate the burden of disease in patients with GPP compared with those with plaque psoriasis, in Japan. This retrospective study was conducted using the Medical Data Vision database between January 1, 2015, and December 31, 2019. Patients with at least one confirmed inpatient or outpatient diagnostic code for GPP (L40.1) or psoriasis vulgaris (L40.0) were included for analysis. The main outcome measures included comparisons of the prevalence of comorbidities, medication use, and healthcare resource utilization between patients with GPP, patients with plaque psoriasis, and a general population-matched cohort. In total, 718 patients with GPP and 27,773 patients with plaque psoriasis were identified. Patients with GPP were more likely to be female than those with plaque psoriasis (51.6% vs. 38.7%). During the 12-month follow-up period, patients with GPP were more likely to experience comorbidities than those with plaque psoriasis, including psoriatic arthritis, other forms of psoriasis, osteoporosis, interstitial pneumonia, and peptic ulcer disease. Medication use also differed between those with GPP and those with plaque psoriasis: patients with GPP were more likely to be prescribed antibiotics and psychiatric medication. Patients with GPP were also more likely to require more healthcare resource utilization with longer hospitalizations than those with plaque psoriasis. Overall, in Japan, patients with GPP have a higher burden of illness than those with plaque psoriasis.

Background Clinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors. Methods In this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 μg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented. Results Sixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (− 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation. Conclusions The low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors. Trial registration The trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020.

Background Much effort has been made to optimize the results of total hip arthroplasty and total knee arthroplasty. With the rapid growth of social media use, mobile apps, such as WeChat, have been considered for improving outcomes and patient satisfaction after total hip arthroplasty and total knee arthroplasty. Objective We aimed to evaluate the effectiveness of a WeChat-based community as an intervention for overall patient satisfaction. Methods The study was conducted among discharged in-hospital patients who received hip or knee procedures in the First Affiliated Hospital of the University of Science and Technology of China from April 2019 to January 2020. An educational online social community was constructed with the WeChat app. Participants willing to join the community were enrolled in a WeChat group and received 3 months of intervention and follow-up. Those who were not willing to use the account were included in a control group and received routine publicity via telephone, mail, and brochures. The Danish Health and Medicine Authority patient satisfaction questionnaire was used to score perioperative patient education and overall satisfaction. The contents in the group chat were analyzed using natural language processing tools. Results A total of 3428 patients were enrolled in the study, including 2292 in the WeChat group and 1236 in the control group. Participants in the WeChat group had higher overall satisfaction scores than those in the control group (mean 8.48, SD 1.12 vs mean 6.66, SD 1.80, P Conclusions The social media–promoted educational community using WeChat was effective among joint replacement patients. Provision of more perioperative education is associated with more active patient participation in the community and therefore more patient satisfaction in terms of the overall joint procedure. Community group chat could facilitate interactions among patients and contribute to overall satisfaction.

Immunotherapies for cancer, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to a long-lasting clinical response. But the therapeutic response rate remains low on account of many tumors that have evolved sophisticated strategies to evade immune surveillance. Solid tumors are characterized by the highly acidic microenvironment, which may weaken the effectiveness of antitumor immunity. Here, we explored a promising therapeutic development deployed by pH manipulation for avoiding immunoevasion. The highly acidified microenvironment of melanoma induces the expression of G-protein-coupled receptor (Ogr1) in T cells, which weakened their effective function and promote tumor growth. Ogr1 inhibition reactivate CD8

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented public health crisis. Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced in SARS-CoV-2-infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue the pneumonia with substantial reduction of viral loads in SARS-CoV-2-infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using the mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention., Graphical abstract, Highlights • S100A8 is dramatically upregulated in SARS-CoV-2-infected animal models and patients • A group of aberrant immature neutrophils is induced during SARS-CoV-2 infection • Immune disorder is mediated by the S100A8/A9-TLR4 pathway • S100A8/A9 inhibitor, Paquinimod, could prevent COVID-19-associated immune disorder, Guo et al. demonstrate that over-activation of S100A8/A9-TLR4 signaling results in immune imbalance and expansion of aberrant immature neutrophils during SARS-CoV-2 infection. Relevant therapeutic targets were validated in animal infection models.

Extracellular acidosis is associated with various immunopathological states. The microenvironment of numerous solid tumours and inflammatory responses during acute or chronic infection are all related to a pH range of 5.5‑7.0. The relationship between inflammation and immune escape, cancer metabolism, and immunologic suppression drives researchers to focus on the effects of low pH on diverse components of disease immune monitoring. The potential effect of low extracellular pH on the immune function reveals the importance of pH in inflammatory and immunoreactive processes. In this review, the mechanism of how pH receptors, including monocarboxylate transporters (MCTs), Na+/H+ exchanger 1, carbonic anhydrases (CAs), vacuolar‑ATPase, and proton‑sensing G‑protein coupled receptors (GPCRs), modulate the immune system in disease, especially in cancer, were studied. Their role in immunocyte growth and signal transduction as part of the immune response, as well as cytokine production, have been documented in great detail. Currently, immunotherapy strategies have positive therapeutic effects for patients. However, the acidic microenvironment may block the effect of immunotherapy through compensatory feedback mechanisms, leading to drug resistance. Therefore, we highlight promising therapeutic developments regarding pH manipulation and provide a framework for future research.

Introduction:Lumbar spinal stenosis (LSS) is caused by structural changes of the spine, which lead to several severe symptoms, including back pain, leg pain, numbness and tingling in the legs, as well as reduced physical function. However, there is little evidence suggesting whether a patient with LSS should be treated with surgery. If surgery is recommended, which type of surgery benefits the patient most? To answer these questions, we will conduct a network meta-analysis and a systematic review to compare surgical and nonsurgical interventions in terms of efficacy as well as safety in adult patients with LSS.Methods and analysis:We will search the PubMed, Cochrane library, and EMBASE databases for articles published prior to October 10, 2019. We will search for randomized controlled trials assessing surgical and nonsurgical interventions for adult patients with degenerative LSS without any language restrictions. The primary outcome measures will be pain and disability. The secondary outcomes will include adverse events (number of events or number of people with each type of adverse event), reoperations, complications, blood loss and operation time. We will obtain the full texts of the potentially relevant studies and independently assess them. The quality of evidence will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation framework. A random-effects network meta-analysis will be performed to analyze all the evidence under the frequentist framework, and the ranking results will be presented. We will generate plots depicting the network geometry using Stata. The network meta-analysis will be performed according to the Bayesian framework. Ethics and dissemination Ethics approval is not required. The research will be published in a peer-reviewed journal.

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Full-endoscopic transforaminal lumbar discectomy (FETD) is increasingly used in patients with lumbar disc herniation (LDH). There is little knowledge on the related factors, including the straight leg raising test (SLR), that influence the operation. Consecutive patients with LDH who came to our hospital from August 2015 to September 2016 and underwent FETD surgery were included. Four kinds of scores, including the VAS (lumbar/leg), ODI and JOA values, were measured and reassessed after FETD to assess the surgical outcomes. There was a statistically significant difference between the scores before surgery and at each postoperative follow-up. In addition, the increase in the JOA score postoperatively was statistically significant compared with that before surgery. There were statistically significant differences among the three subpopulations [patients considered SLR positive (0°–30°), SLR positive (31°–60°) and SLR negative (61°–)] in the changes in the VAS (leg), ODI and JOA values. However, there were no statistically significant differences among the three subpopulations [patients considered SLR positive (0°–30°), SLR positive (31°–60°) and SLR negative (61°–)] in the changes in VAS score (lumbar). FETD showed great effectiveness in treating patients with lumbar disc herniation. Patients who were SLR negative may receive greater benefit from FETD.

Background: Pathologic processes in Creutzfeldt-Jakob disease (CJD) are not fully understood. Familial CJD (fCJD) gives opportunities to discover pathologic changes in the preclinical stage. Objective: To investigate cerebral glucose metabolism in the preclinical stage via 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in fCJD. Methods: Seven asymptomatic carriers of G114V mutation and six family members without PRNP mutation from the same fCJD kindred were included, and were followed for 2 years. Ten symptomatic CJD patients were also recruited. All subjects underwent standardized clinical examinations and 18F-FDG PET scans. Results were compared in three groups: baseline carriers against non-carriers (baseline analysis), changes after 2 years in carriers (follow-up analysis), and differences between symptomatic CJD patients and healthy controls (CJD patients analysis). Results: No carriers developed any neurological symptoms during 2-year follow-up. Baseline analysis: carriers demonstrates decreased metabolism (p

Background Conventional paired meta-analyses have shown inconsistent results regarding the safety and efficacy of different interventions. Objective To perform a network meta-analysis (NMA) and systematic review based on randomized controlled trials (RCTs) evaluating the efficacies of different interventions for lumbar spinal stenosis (LSS). Methods We searched PubMed, Embase, Cochrane Library, Web of Science, and major scientific websites from inception to October 10, 2019, for randomized controlled trials comparing the nine most commonly used interventions for LSS. The main outcomes were disability and pain intensity. The PROSPERO number was CRD42020154247. Results First, laminotomy was better in improving patients’ short- and long-term dysfunction (probability 49% and 25%, respectively). Second, decompression, decompression plus fusion, endoscopic decompression, interspinous process spacer device implantation, laminectomy, laminotomy and minimally invasive decompression were significantly more efficacious in relieving pain than non-surgical interventions (mean difference in the short-term −21.82, −22.00, −16.68, −17.47, −17.75, −17.61 and −18.86; in the long-term −37.14, −34.04, −34.07, −39.79, −36.14, −32.75 and −39.14, respectively). Third, endoscopic decompression had a lower complication rate (probability 51%). In addition, laminotomy had a lower reoperation rate (probability 45%). Fourth, decompression plus fusion resulted in more blood loss than any other surgical intervention (probability 96%). Finally, endoscopic decompression had the shortest hospitalization time (probability 96%). Conclusions There were no significant differences among the different interventions in improving patient function. Surgical interventions were associated with better pain relief but a higher incidence of complications. Decompression plus fusion is not necessary for patients. In addition, endoscopic decompression as a novel and less invasive surgical approach may be a good choice for LSS patients.

Comprehensive genomic testing will be required to identify appropriate targets for the precision therapy of breast cancer. Although RNA sequencing (RNA-seq) is an unparalleled platform for this purpose, existing molecular-based prognostic signatures are not optimal for RNA-seq data. In this study, we analyzed RNA-seq datasets to generate a novel prognostic gene signature for breast cancer patients. RNA-seq and clinical datasets from breast cancer patients were obtained from The Cancer Genome Atlas and randomly assigned to training (

Atrial fibrillation (AF) is one of the most common types of arrhythmias and often leads to clinical complications. The objectives of this study were to offer insights into the metabolites of AF and to determine biomarkers for AF diagnosis or prediction. Sixty atrial appendage samples (AF group: 30; non-AF group: 30) and 163 plasma samples (AF group: 48; non-AF group: 115) from 49 AF patients and 116 non-AF patients were subjected to liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) metabolomics analysis. Consequently, 24 metabolites in atrial appendage samples and 24 metabolites in plasma samples were found to reflect metabolic differences between AF and non-AF patients (variable importance in projection (VIP) ≥ 1, P ≤ 0.05). Five identical metabolites including creatinine, D-glutamic acid, choline, hypoxanthine, and niacinamide (VIP ≥ 1.5, P

The BIG Data Center at Beijing Institute of Genomics (BIG) of the Chinese Academy of Sciences provides a suite of database resources in support of worldwide research activities in both academia and industry. With the vast amounts of multi-omics data generated at unprecedented scales and rates, the BIG Data Center is continually expanding, updating and enriching its core database resources through big data integration and value-added curation. Resources with significant updates in the past year include BioProject (a biological project library), BioSample (a biological sample library), Genome Sequence Archive (GSA, a data repository for archiving raw sequence reads), Genome Warehouse (GWH, a centralized resource housing genome-scale data), Genome Variation Map (GVM, a public repository of genome variations), Science Wikis (a catalog of biological knowledge wikis for community annotations) and IC4R (Information Commons for Rice). Newly released resources include EWAS Atlas (a knowledgebase of epigenome-wide association studies), iDog (an integrated omics data resource for dog) and RNA editing resources (for editome-disease associations and plant RNA editosome, respectively). To promote biodiversity and health big data sharing around the world, the Open Biodiversity and Health Big Data (BHBD) initiative is introduced. All of these resources are publicly accessible at http://bigd.big.ac.cn.

microRNAs (miRs) have recently emerged as small non-coding regulators of gene expression. We performed a loss-of-function screening by recruiting retrovirus mediated arbitrary manipulation of genome coupled with escape of cells from 5-Aza-2′-deoxycytidine (5-Aza-dC)-induced senescence. miRNA pool from cells that emerged from 5-Aza-dC-induced senescence was subjected to miR-microarray analysis with respect to the untreated control. We identified miR-451 as one of the upregulated miRs and characterized its functional relevance to drug resistance, cell growth, tumor suppressor proteins p53 and pRb, and stress response. We report that miR-451 caused growth arrest in cells leading to their resistance to 5-Aza-dC-induced senescence. Decrease in cyclin D1, CDK4 and phosphorylated pRB supported the growth arrest in miR-451 transfected cells. We demonstrate that Collaborator of ARF (CARF) protein is a new target of miR-451 that intermediates its function in tumor suppressor and stress signaling.

The HECT E3 ligase Smurf1 (Smad ubiquitination regulatory factor 1) plays a critical role in several important biological pathways by targeting many proteins for ubiquitination and degradation, such as Smad1/5, MEKK2 and RhoA. However, the function of Smurf1 in metaphase-to-anaphase transition remains unclear. Here, we show that Smurf1 interacts with and targets Securin, an inhibitor of sister-chromatid separation, for poly-ubiquitination and proteasomal degradation. Further results demonstrate that Securin is a physiological substrate of Smurf1 in MEF cells. Knockdown of Smurf1 results in sister-chromatid separation inhibition and delay of anaphase onset. This study provides the first evidence that Smurf1 functions as a novel regulator for the metaphase-to-anaphase transition.